Complex structure of electrophysiological gradients emerging during long-duration ventricular fibrillation in the canine heart

Abstract

Long-duration ventricular fibrillation (LDVF) in the globally ischemic heart is a common setting of cardiac arrest. Electrical heterogeneities during LDVF may affect outcomes of defibrillation and resuscitation. Previous studies in large mammalian hearts have investigated the role of Purkinje fibers and electrophysiological gradients between the endocardium (Endo) and epicardium (Epi). Much less is known about gradients between the right ventricle (RV) and left ventricle (LV) and within each chamber during LDVF. We studied the transmural distribution of the VF activation rate (VFR) in the RV and LV and at the junction of RV, LV, and septum (Sep) during LDVF using plunge needle electrodes in opened-chest dogs. We also used optical mapping to analyze the Epi distribution of VFR, action potential duration (APD), and diastolic interval (DI) during LDVF in the RV and LV of isolated hearts. Transmural VFR gradients developed in both the RV and LV, with a faster VFR in Endo. Concurrently, large VFR gradients developed in Epi, with the fastest VFR in the RV-Sep junction, intermediate in the RV, and slowest in the LV. Optical mapping revealed a progressively increasing VFR dispersion within both the LV and RV, with a mosaic presence of fully inexcitable areas after 4-8 min of LDVF. The transmural, interchamber, and intrachamber VFR heterogeneities were of similar magnitude. In both chambers, the inverse of VFR was highly correlated with DI, but not APD, at all time points of LDVF. We conclude that the complex VFR gradients during LDVF in the canine heart cannot be explained solely by the distribution of Purkinje fibers and are related to regional differences in the electrical depression secondary to LDVF.

Fig. 1.

Schematic representation of the mapping modalities used in this study. A: approximate positions of the plunge needle electrodes. RV1, RV2, and RV3 indicate electrodes in the right ventricle (RV). LV1, LV2, and LV3 indicate electrodes in the left ventricle (LV). The electrode in the anterior projection of the interventricular septum (Sep) is also shown. All electrodes were in the transverse plane located at approximately middistance between the base and apex. The epicardial (Epi) and midmyocardial (Mid) leads in the plunge needle electrodes are indicated, as is the endocardial (Endo) lead in the RV and LV electrodes. Deep indicates the lead in the Sep electrode that is the most distant electrode from Epi and is located in the depth of Sep. See text for more detail. B–D: three positions of the imaged area (circles) used in the optical mapping experiments. B: the imaged area mostly covers the LV with a narrow region of the RV. C: the imaged area covers approximately equal portions of the RV and LV. D: the imaged area mostly covers the RV with a narrow region of the LV. LAD, left anterior descending coronary artery.

Fig. 2.

Unipolar electrograms recorded from different leads of plunge needle electrodes during long-duration ventricular fibrillation (LDVF) in a representative experiment. Top: 0 min of LDVF; bottom: 10 min of LDVF. Shown are recordings from the RV3 (left), Sep (middle), and LV3 (right) electrodes. See Fig. 1A for electrode locations and other definitions.

Fig. 3.

Time course of VF activation rate (VFR) in a matrix of 3 × 3 of nine principal locations (LV Endo, LV Mid, LV Epi, Sep Deep, Sep Mid, Sep Epi, RV Endo, RV Mid, and RV Epi) during 0–9 min of LDVF. Colors indicate different wall types (LV, red; Sep, green; RV, blue). Symbols indicate different distances from Epi (Endo, triangles; Mid, squares; Epi, circles; Sep Deep, ×). A–C: the nine VFR curves grouped by wall type (LV, Sep, and RV, respectively). D–F: the same nine VFR curves grouped by distance from Epi (Epi, Mid, and Endo/Deep, respectively). *Statistically significant difference between the VFR curves by two-way ANOVA. G: summary of statistically significant differences in VFR time courses between different locations.

Fig. 4.

Epicardial distribution of VFR during LDVF in five experiments in situ (A–E). Lighter shades of grey indicate higher VFR. Note that in all experiments there is a local maximum in Epi VFR distribution either in the Sep or adjacent RV position (RV1) after 3–4 min of LDVF.

Fig. 5.

Examples of VFR distribution measured in Epi optical maps in isolated hearts at the early and late stages of LDVF. A: experiment with predominantly LV optical mapping. Top, VFR maps at 0 min (right) and 8 min (left) of LDVF. Bottom, single-pixel recordings from sites a–c (indicated on the respective VFR maps with circles). B: experiment with predominantly RV optical mapping. Top, VFR maps at 0 min (right) and 10 min (left) of LDVF. The arrow in the 10-min map indicates a thin inexcitable area (black, VFR = 0) separating two active areas (green, VFR∼ 6 Hz; blue, VFR ∼ 3 Hz). Bottom, the same layout as in A. C: single-pixel recordings of sites a and c from B shown with an expanded time scale. Note the fixed 2:1 phase relationship between activations in these two locations, suggesting that sites a and c have a common source of excitation even though they do not communicate within the imaged area. Note the extremely high level of VFR heterogeneity in both the RV and LV at the advanced stages of LDVF.

Fig. 6.

Right-to-left differences in the time courses of VFR (A), diastolic interval (DI; B), action potential duration (APD; C), and percentage of excitable area (D) in Epi optical maps during LDVF. *Statistically significant difference between respective curves by two-way ANOVA.

Fig. 7.

A and B: scatterplots of VF cycle length (VFCL) measured in the RV and LV at all time points of LDVF versus DI (A) and APD (B). There was a strong direct correlation between VFCL and DI (A) and a weak inverse correlation between VFCL and APD (B).

Fig. 8.

Examples of transitions between the focal and reentrant pattern in the RV at the late stages of LDVF. A: individual frames of a phase movie at 8 min of LDVF. In 1, several singularity points coexist in the mapped area; the point indicated by the white arrow is the leading source of activation in the mapped area for at least seven cycles. In 2, the reentrant source is replaced by a repetitive focal source in approximately the same location (black arrows). In 3, the focal source has reverted back to a repetitive reentrant source (white arrow) in approximately the same location. B: activation map at 10 min of LDVF showing a stable focal pattern (black arrows) in the same location as the focal and reentrant sources shown in A,1–3. This focal source activates the RV but not the LV. The LV is activated by a planar wave (white arrow), which is apparently unrelated to the source in the RV. Red, early activation; magenta, late activation. The red front in the basal RV (B, top) shows the excitation wave generated in the previous cycle that is exiting the field of view when a new focal wave emerges. C: unique example of stable Epi reentry in the RV (white arrow) at a very late stage of LDVF (16 min). D: approximate locations of repetitive breakthrough patterns observed in 7 of 10 hearts.